Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia: Implications for Neuro-COVID.
Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia: Implications for Neuro-COVID.
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DOI：
10.1007/s11481-021-10015-6
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Mahajan SD
中科院分区：
文献类型：
--
作者：
Clough E;Inigo J;Chandra D;Chaves L;Reynolds JL;Aalinkeel R;Schwartz SA;Khmaladze A;Mahajan SD
来自当前COVID-19大流行的新临床数据表明，约40%的COVID-19患者出现归因于病毒性脑炎的神经系统症状，而在COVID长途运输者中，慢性神经炎症和神经元损伤导致被描述为神经COVID的综合征。我们假设SAR-COV 2诱导线粒体功能障碍和细胞依赖性内在凋亡途径的激活，导致小胶质细胞和神经元凋亡。我们的研究目的是确定SARS-COV 2对线粒体生物合成的影响，并使用拉曼光谱技术在真实的时间内非侵入性地监测人类小胶质细胞中的细胞凋亡，提供活细胞中线粒体功能的独特时空信息。我们用SARS-COV 2刺突蛋白处理人小胶质细胞，检测细胞因子和活性氧（ROS）产生的水平，确定SARS-COV 2对线粒体生物合成的影响，并检测磷脂分子组成的变化。我们的研究结果表明，SARS-COV 2刺突蛋白增加促炎细胞因子和ROS产生的水平，增加凋亡，并增加小胶质细胞的耗氧率（OCR）。OCR的增加指示增加的ROS产生和氧化应激，表明SARS-COV 2诱导细胞死亡。拉曼光谱产生了磷脂如磷脂酰肌醇（PI）、磷脂酰丝氨酸（PS）、磷脂酰乙醇胺（PE）和磷脂酰胆碱（PC）的显著差异，其占SARS-COV 2处理和未处理的小胶质细胞之间线粒体膜脂质的约80%。这些数据为SARS-COV 2诱导的线粒体功能障碍提供了重要的机制见解，线粒体功能障碍是与Neuro-COVID相关的神经病理学的基础。
Emerging clinical data from the current COVID-19 pandemic suggests that ~ 40% of COVID-19 patients develop neurological symptoms attributed to viral encephalitis while in COVID long haulers chronic neuro-inflammation and neuronal damage result in a syndrome described as Neuro-COVID. We hypothesize that SAR-COV2 induces mitochondrial dysfunction and activation of the mitochondrial-dependent intrinsic apoptotic pathway, resulting in microglial and neuronal apoptosis. The goal of our study was to determine the effect of SARS-COV2 on mitochondrial biogenesis and to monitor cell apoptosis in human microglia non-invasively in real time using Raman spectroscopy, providing a unique spatio-temporal information on mitochondrial function in live cells. We treated human microglia with SARS-COV2 spike protein and examined the levels of cytokines and reactive oxygen species (ROS) production, determined the effect of SARS-COV2 on mitochondrial biogenesis and examined the changes in molecular composition of phospholipids. Our results show that SARS- COV2 spike protein increases the levels of pro-inflammatory cytokines and ROS production, increases apoptosis and increases the oxygen consumption rate (OCR) in microglial cells. Increases in OCR are indicative of increased ROS production and oxidative stress suggesting that SARS-COV2 induced cell death. Raman spectroscopy yielded significant differences in phospholipids such as Phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC), which account for ~ 80% of mitochondrial membrane lipids between SARS-COV2 treated and untreated microglial cells. These data provide important mechanistic insights into SARS-COV2 induced mitochondrial dysfunction which underlies neuropathology associated with Neuro-COVID.
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影响因子：
24.1
作者：
Bertheloot D;Latz E;Franklin BS
通讯作者：
Franklin BS
影响因子：
9
作者：
Channappanavar R;Perlman S
通讯作者：
Perlman S
影响因子：
15.9
作者：
Bhardwaj, N;Seder, RA;Feldman, MV
通讯作者：
Feldman, MV
影响因子：
5.3
作者：
Gonçalves de Andrade E;Šimončičová E;Carrier M;Vecchiarelli HA;Robert MÈ;Tremblay MÈ
通讯作者：
Tremblay MÈ
DOI：
10.1134/s0006297920120068
发表时间：
2020-12
期刊：
Biochemistry. Biokhimiia
影响因子：
--
作者：
Chernyak BV;Popova EN;Prikhodko AS;Grebenchikov OA;Zinovkina LA;Zinovkin RA
通讯作者：
Zinovkin RA